Our research program focuses on the structure and mechanism of heme- and metal-containing proteins, the mechanism of action of antitumor drugs and on noninvasive NMR studies of intact cells and tissues. In the area of enzymes and proteins we propose to study the mechanism of cooperative oxygenation of hemoglobin, the mechanism of intracellular polymerization of sickle hemoglobin, the spatial arrangement and conformation of substrates at the catalytic sites of phosphoryl transfer enzymes, the role of metal ions in the catalysis of phosphoryl transfer, the mechanism of carbonic anhydrase action, and the electron transfer mechanism of cytochrome c. In the are of antitumor drugs, we propose to study the structure and mechanism of two peptide antitumor antibiotics, bleomycin and neocarzinostatin. In our noninvasive NMR work with intact cells and tissues, we propose to study the effect of insulin on cellular ion-transport processes, the mechanism of mitogenic effects of insulin, and a possible regulatory role of ionized magnesium in cellular growth and metabolism. Magnetic resonance spectroscopy is the major tool used in all our studies. A secondary objective of our research is the development of new methodology and/or refinement of existing magnetic resonance methods for the study of biological systems.